At the present time, non-steroidal anti-inflammatory drugs are comprised of two categories, one the carboxylic acid, and the other enolic acid. Carboxylic acid type non-steroidal anti-inflammatory drugs are easily metabolized in the body, or conjugated with glucuronic acid and promptly excreted in the urine, resulting in a short half-life. Among this type of non-steroidal anti-inflammatory drugs, whose structures containing oxicam are easily absorbed, but hepatic metabolism and renal clearance are slower. Piroxicam(4-hydroxyl-2-methyl-N-(2-pyridyl)-2H-1,2-benzo-thiazine- 3-carboxamide-1,1-dioxide) belongs to this category, and its side effect is long recognized to be less than other non-steroidal anti-inflammatory drugs in the same category. In addition to piroxicam, other oxicams include isoxicam, sudoxicam, cinnoxicam, tenoxicam, and lomoxicam. They have anti-inflammatory, anti-pyretic and analgesic effects, but do not have typical side effects of narcotic analgesic drugs, such as breath suppression, and addiction. Therefore, these non-steroidal anti-inflammatory drugs are classified as non-narcotic analgesies. Non-steroidal anti-inflammatory drugs are extensively used in clinical treatment, since they can relieve mild to moderate pain, lower body temperature, reduce inflammatory symptoms, and prevent or relieve gout.
According to reports revealed by Brogden R. N. et al. in 1981 Drugs, volume 22, page 165 to 187, piroxicam possessed a linear pharmacokinetic property. Regardless of whether single or multiple doses were administered to patients, the maximum plasma concentration(Cmax) and area under the curve(AUC) are proportional to the dose administered. Results from experiments of the oral, rectal, and intravenous routes in rats and rabbits showed that oral administration of piroxicam was almost completely absorbed. Since piroxicam is a weak acid, it is in the non-ionized form while in the stomach. According to reports by Benveniste C. et al. revealed in 1985 Eur. J. Clin. Pharmacol. volume 38, page 547 to 549, oral administration of piroxicam shows a maximum plasma concentration after two hours, and then shows a second maximum plasma concentration due to hepatic and intestinal recycling.
In recent years, pharmaceutical development has focused on dosage forms that could bypass the gastrointestinal tract and liver, in order to avoid the first pass effect, or gastrointestinal side effects. Meanwhile the plasma concentration could be constantly maintained. Among these dosage forms, a transdermal delivery system has been shown to release the drug constantly, and delivers it into capillary vessels upon penetration through the skin, resulting in reaching the target area and producing a therapeutic effect. In addition, a transdermal drug delivery system is more convenient than other dosage forms, since the patch can be removed at any time, which may avoid emergency situations due to dose dumping. For an adult, the total area of the skin is 2 M.sup.2, and capillary vessels possess one third of blood flow. For these reasons, transdermal drug delivery system has a potential future.
For transdermal drug delivery, physical-chemical properties of drug such as partition coefficient, molecular weight, size, concentration, and polarity may affect the result of delivery. Other factors such as polarity of transdermal base, solubility of drug in the transdermal base, compositions in the base, viscosity, pathologic and physiological conditions of the skin: hydration condition, and skin temperature, as well as the position of patch placement all may affect the result of drug delivery. However, the most difficult problem at the present time is the lack of potent and safe transdermal absorption enhancers.
One of the recent advances in oriental medicine was the fact that the Japanese Ministry of Health agreed in 1975 to include 210 Chinese herbal medicines in the nation-wide health insurance program. Among these, Glycyrrhizae Radix had the highest rate of usage, 71.4%. Others in descending rank were: Zingiberis Rhizoma 42.9%, Hoelen 35.2%, Paeoniae Radix 32.9%, Zizyphi Fructus 31.9%, and Cinnamoni Cortex et Caulis 29.5%. In the second edition of the Japanese National Formulary, the highest rate of usage remained Glycyrrhizae Radix, the second highest was Zingiberis Rhizoma, and others were similar to past usage.
In Chinese herb formulas, the following herbs have high frequencies of usage. They are Glycyrrhizae Radix, Enzoinum, Cinnamoni Cortex et Caulis, Zingiberis Rhizoma, Zizyphi Fructus, Zedoariae Rhizoma, Magnoliae Flos, Foeniculi Fructus, Cardamomi Fructus, Eucalypti Folium, Zanthoxylic Fructus, Lupuli Strobilus, Magnoliae Cortex, Cinae Flos, Perillae Herba, Valerianae Radix, Asari Herba cum Radice, Amomi Cardamomi Fructus, Myristicae Semen, Menthae Herba, Digitalis Folium, Benzonium, Corni Fructus, Piperis Fructus, Hoelen, Polyporus, Ergota, Ephedrae Herba, Platycodi Radix, Caryophylli Flos, Bufonis Venenum, Schizonepetae Herba, Citri Exocarpium, Aurantii Fructus Immaturus, Rhei Rhizoma, Arecae Semen, Gambir, etc.. The amount or composition of the natural products in these Chinese herbs may be varied due to the area where grown and seasons of harvest.
These herbs usually contain monoterpinoid glycosides, triterpinoid glycosides, triterpinoid saponins, tannin, and volatile oils. They are all bioactive. Triterpinoid glycosides may lower the surface tension of the skin, which helps drug to penetrate to deeper tissues, and results in higher therapeutic effects. Volatile oil, and glycyrrhizin are proven to have an anti-inflammatory effect. Furthermore, Glycyrrhizin can inhibit paw swelling.